Nevin Manimala

Discov Oncol. 2026 Apr 30. doi: 10.1007/s12672-026-05086-x. Online ahead of print.

ABSTRACT

BACKGROUND: Chordoma is a rare malignant bone tumor with limited effective systemic treatment options. Conventional chemotherapy generally shows minimal benefit, highlighting the need for predictive preclinical models to explore therapeutic vulnerabilities. Patient-derived organoids (PDOs) have emerged as a promising three-dimensional culture system that preserves tumor architecture and molecular features while enabling functional testing. However, mechanistic studies linking pathway activity to drug response in chordoma PDOs remain limited.

METHODS: Fresh surgical specimens from five patients with primary spinal chordoma were used to attempt generation of three-dimensional PDO cultures, of which primary three-dimensional cultures were successfully established. Organoids were characterized by histology, immunohistochemistry, and quantitative PCR analysis of chordoma-associated markers. Functional drug screening was performed using a panel of clinically relevant agents in a representative PDO model, followed by dose-response testing of gemcitabine. The role of TP53 in drug response was examined using small interfering RNA-mediated knockdown, with assessment of cell viability, Ki-67 expression, and DNA-damage response-related proteins. Statistical analyses were performed using one-way analysis of variance, with p < 0.05 considered statistically significant.

RESULTS: The established PDOs recapitulated the histopathological and molecular characteristics of their matched primary tumors and maintained stable growth across six passages. Among the screened agents, gemcitabine showed the strongest growth-inhibitory effect in PDO-based functional assays. Dose-response experiments confirmed significant gemcitabine-induced growth suppression. Importantly, TP53 knockdown markedly attenuated gemcitabine-induced cytotoxicity, increased proliferative activity, and reduced activation of DNA-damage response signaling, indicating a TP53-dependent vulnerability.

CONCLUSIONS: This study establishes a spinal chordoma PDO platform for functional precision oncology. Our findings identify a TP53-dependent DNA-damage vulnerability engaged by gemcitabine in patient-derived three-dimensional models, supporting biomarker-informed hypothesis generation rather than routine chemotherapy in unselected patients. This PDO-based approach provides a translational framework for exploring pathway-defined therapeutic susceptibilities in rare tumors such as chordoma.

PMID:42060212 | DOI:10.1007/s12672-026-05086-x

Mol Biol Rep. 2026 Apr 30;53(1):702. doi: 10.1007/s11033-026-11884-x.

ABSTRACT

A central enigma in crop improvement lies in introducing beneficial traits without fitness trade-offs. Rice, the cornerstone of global food security, demands multifaceted genetic innovation to sustain yield, quality, and resilience in the face of mounting climatic constraints. With the global population projected to surpass ten billion, functional master regulators such as miRNAs stand out as transformative molecular tools, capable of orchestrating complex trait networks and offering a tangible path toward the next green revolution. These are robust fine-tuners that orchestrate a myriad of functional processes and provide a value addition in emerging technologies such as assisted breeding, genome editing, and genomic selection to make rice production feasible. Herein, we have provided a comprehensive synthesis and updates on functional miRNA-mediated agronomically advantageous trait improvement exclusively for rice. It represents the latest functional understanding of miRNAs and their involvement as signatures of domestication and divergence processes, in support of the previously established notion and recent updates on emerging miRNA-assisted resources and technologies, such as their application as artificial solutions for improving genotypes, coding, and dietary potentialities for environmental safeguards and innovative biotherapeutics. Recent updates signify their robust cross-kingdom communicators’ potential for multifaceted non-host dialoguing, and their integrative action relies on the coordination with other non-coding regulatory elements for various downstream trait regulation. Moreover, specific highlights refer to the application of miRNAs for rice agronomical trait improvements, broadly classified into three functional domains, viz., biotic and abiotic stresses and yield and quality traits. Such updated functional aspects of different miRNA modules would strengthen rice improvement by facilitating a foundation and future roadmap for miRNA-mediated trait discovery and improvement.

PMID:42060211 | DOI:10.1007/s11033-026-11884-x

J Neurol. 2026 Apr 30;273(5):297. doi: 10.1007/s00415-026-13839-5.

ABSTRACT

INTRODUCTION: This study aimed to identify neuropsychiatric, motor, and cognitive features associated with accelerated disease progression in behavioral variant frontotemporal dementia (bvFTD).

METHODS: 192 participants were classified as having mild or moderate disease severity based on CDR + NACC FTLD global scores, with scores of 0.5 or 1.0 defined as mild (n = 106) and 2.0 as moderate (n = 86). Participants were further categorized as having accelerated (mild: n = 35; moderate: n = 32) or non-accelerated (mild: n = 71; moderate: n = 54) progression rates based on change in CDR + NACC FTLD-SB sum of boxes (SB) scores (≥ 3.5 points) between Visit 1 and 2. Random forest modeling and logistic regression identified features most predictive of accelerated progression within each group.

RESULTS: In mild bvFTD, episodic memory impairment and presence of frontal-behavioral neuropsychiatric symptoms were predictive of accelerated progression, whereas in moderate bvFTD, language impairments and motor signs were the strongest predictors. Identified features improved prediction of accelerated progression beyond demographic and clinical factors in mild (∆R2 = .22, p < 0.001) and moderate bvFTD (∆R2 = 0.11, p = 0.08) but did not achieve statistical significance in the moderate group.

DISCUSSION: Distinct clinical profiles predict accelerated progression in mild versus moderate bvFTD, underscoring the importance of stage-specific clinical markers for prognosis and care.

PMID:42060164 | DOI:10.1007/s00415-026-13839-5

Int J Nurs Knowl. 2026 Apr 30:20473087261443269. doi: 10.1177/20473087261443269. Online ahead of print.

ABSTRACT

PurposeThis study was designed to evaluate the process of controlling body temperature in patients who were diagnosed with infection and followed up with the diagnosis of “hyperthermia” according to the NANDA-I nursing diagnosis classification according to the outcome criterion “NOC (0800) Thermoregulation Assessment.”MethodThis methodological and descriptive study was conducted with 102 inpatients followed up with the nursing diagnosis of “hyperthermia” in the Department of Infectious Diseases and Clinical Microbiology of a training and research hospital between June 2024 and June 2025. The data were collected using the “Patient Information Form” and the “NOC (0800) Thermoregulation Assessment Scale.” Statistical analyses specific to groups that were normally distributed (t-test) or not (Mann-Whitney U, Kruskal-Wallis, and Spearman correlation analysis) were done to analyze the data. For validity and reliability, the Davis Technique, Cronbach’s α coefficient, Standardized Root Mean Square Residual fit indices, and item-total correlation statistical analyses were done.FindingsThe content validity index of the NOC scale was calculated as 0.97. When the mean scores of the patients on the NOC (0800) Thermoregulation Assessment Scale were analyzed, a statistically significant difference was observed for repeated assessments (p < 0.01). The indicators “dropped skin temperature”, “hypothermia”, “heat cramps”, “heat stroke”, and “cold-related tissue damage” were “not applicable” in the study population. No statistically significant difference was found between the NOC scale mean scores of the patients according to their gender, marital status, educational level, occupation, and presence of chronic diseases (p > 0.05).ConclusionsThe Turkish version of the NOC (0800) Thermoregulation Assessment Scale was a valid tool that could be used during the process of controlling body temperature in patients with infection.Implications of nursing practiceThe use of the NOC (0800) Thermoregulation Assessment Scale would create a common language for delivering nursing care while assessing the process of controlling body temperature.

PMID:42060139 | DOI:10.1177/20473087261443269

Calcif Tissue Int. 2026 Apr 30;117(1):72. doi: 10.1007/s00223-026-01537-3.

ABSTRACT

Although α-Klotho has gained attention as a promising biomarker of aging, its association with frailty and broader aging-related outcomes beyond chronic kidney disease-mineral and bone disorder remains incompletely characterized. This systematic review and meta-analysis aimed to investigate the association between circulating α-Klotho levels and aging-related outcomes, including frailty, effects of physical activity and exercise interventions, body composition, cognitive and neuropsychiatric status, sarcopenia, and bone mineral density (BMD). A comprehensive literature search was performed across multiple electronic databases, including Ovid MEDLINE, Web of Science, Scopus, PubMed, and the Cochrane Library, to identify relevant studies published up to April 30, 2025. Pooled analyses were conducted using random-effects models, with effect estimates synthesized as mean differences, odds ratios, or correlation coefficients, and heterogeneity assessed using the I² statistic. Risk of bias was assessed using design-specific tools, including the Newcastle-Ottawa Scale, the Risk of Bias 2 tool (RoB2) of the Cochrane collaboration, and the Joanna Briggs Institute (JBI) checklists. A total of 109 studies met the inclusion criteria and were included. In our meta-analysis, higher circulating α-Klotho levels were significantly associated with lower odds of frailty (OR = 0.61, 95% CI: 0.49, 0.77; p < 0.0001, I² = 0%). Exercise interventions increased circulating α-Klotho (95% CI: 93.93, 261.73, p < 0.0001; I² = 89%), but habitual physical activity showed no significant effect on α-Klotho compared to inactive controls (p = 0.25; I² = 100%). Lower circulating α-Klotho levels were observed in individuals with osteoporosis compared with those with normal BMD (95% CI: – 114.98, – 25.49; p = 0.002) and in individuals with osteopenia compared with those with normal BMD (95% CI: – 123.22, – 0.74; p = 0.05), and were associated with fractures. Based on qualitative synthesis, circulating α-Klotho levels were positively associated with multiple physical function outcomes, including grip strength, short physical performance battery scores, and sit-to-stand performance, with mixed findings for gait speed and the 6-min walk test. Circulating α-Klotho appears to be a promising biomarker for frailty, physical function, and bone health in aging; however, evidence for cognitive outcomes remains limited and inconsistent. Substantial heterogeneity and the observational nature of most studies highlight the need for more standardized and longitudinal research.

PMID:42060134 | DOI:10.1007/s00223-026-01537-3

Eur J Trauma Emerg Surg. 2026 Apr 30;52(1):154. doi: 10.1007/s00068-026-03192-7.

ABSTRACT

BACKGROUND: Coronal shear fractures of the distal humerus are rare but severe injuries. Reconstruction is often challenging, especially in comminuted cases, which is why many surgeons opt for an elbow arthroplasty in those cases. However, total elbow arthroplasty is associated with a variety of potential problems itself. Therefore, the aim of this study was to present the functional and clinical outcome of coronal shear fractures treated by osteosynthetic reconstruction in a short- to mid-term follow-up, and to identify possible risk factors for an inferior outcome.

METHODS: We performed a retrospective follow-up assessment of 51 consecutive patients (30 women; median age 56 years, (IQR 39-62)) who underwent osteosynthetic reconstruction for coronal shear fractures between 2012 and 2022 after a minimum follow-up period of two years. The Mayo Elbow Performance Score, Oxford Elbow Score, and Disabilities of the Arm, Shoulder and Hand score were evaluated, and all available radiographs were analyzed. All complications and revision procedures were assessed. Univariable and multivariate regression analyses were performed to identify potential risk factors for a poor outcome following osteosynthetic reconstruction.

RESULTS: After a median follow-up period of 43 (IQR 28-78) months, the median Mayo Elbow Performance Score was 100 (IQR 85-100), the median Oxford Elbow Score was 42 (IQR 34-46), and median Disabilities of the Arm, Shoulder and Hand score was 6 (IQR 2-28). The median ROM was 148° (IQR 126-155) for flexion, 0° (IQR 0-0) for extension, 90° (IQR 85-90) for pronation, and 90° (IQR 85-90) for supination. There was no extension deficit on the injured site. The overall complication and reoperation rates were 35.3% and 27.4%, respectively, with severe elbow stiffness being the most common reason for revision. Increasing Dubberley classification and posterior comminution were significantly associated with a poor outcome and higher rates of complications and revision.

CONCLUSION: This short- to mid-term follow-up shows good functional results after osteosynthetic reconstruction in coronal shear fractures despite high complication and revision rates. However, increasing Dubberley classification, posterior comminution and the presence of complications show inferior outcome scores. This study shows that osteosynthetic reconstruction can be an option even in comminuted coronal shear fractures. Nevertheless, patient factors need to be considered and an individual decision concerning the surgical treatment is necessary. Patients should be counseled about the high complication rates and inferior outcome with increasing Dubberley classification.

LEVEL OF EVIDENCE: Level III.

PMID:42060120 | DOI:10.1007/s00068-026-03192-7

Clin Transl Oncol. 2026 Apr 30. doi: 10.1007/s12094-026-04371-z. Online ahead of print.

ABSTRACT

BACKGROUND/OBJECTIVES: Chemotherapy-induced peripheral neuropathy (CIPN) is a frequent toxicity of neurotoxic agents commonly used in colorectal cancer (CRC) and has limited evidence-based management options. Exercise may help, but the optimal prescription during chemotherapy remains uncertain. To evaluate the effects of an eight-week exercise program on CIPN (primary outcome), cancer-related fatigue (CRF), handgrip strength, and physical activity in CRC patients receiving chemotherapy.

METHODS: This pilot parallel-group randomized controlled trial screened 44 CRC patients receiving chemotherapy; 40 were randomized (1:1) to an intervention group (supervised resistance training twice weekly plus home-based aerobic exercise) or a control group (home-based physical activity program only). Outcomes were assessed at baseline and after eight weeks. NCT06404359.

RESULTS: Twenty-seven participants completed follow-up (intervention n = 15; control n = 12). Baseline characteristics were comparable. No statistically significant between-group differences were observed for CIPN, CRF, or handgrip strength. Physical activity increased significantly in the intervention group compared with controls (p < 0.001). Adherence exceeded 80%, and no exercise-related adverse events were reported.

CONCLUSIONS: In this pilot trial, an eight-week program combining supervised resistance training with home-based aerobic exercise was feasible and safe and increased self-reported physical activity, but did not demonstrate statistically significant improvements in CIPN, fatigue, or strength compared with home-based aerobic exercise alone. Larger adequately powered trials are warranted.

PMID:42060079 | DOI:10.1007/s12094-026-04371-z

Malays J Pathol. 2026 Apr;48(1):115-123.

ABSTRACT

INTRODUCTION: Several MLLT10-associated single-nucleotide polymorphisms (SNPs) have been identified by genome-wide association studies (GWASs) as germline risk variants for meningioma in predominantly European cohorts, but their relevance in Koreans remains uncertain. We investigated these MLLT10 risk SNPs in Korean meningiomas, assessing differences across two time cohorts and comparing allele frequencies with those observed in other populations.

MATERIALS AND METHODS: Three MLLT10 SNPs (rs12770228, rs11012732, and rs1243180) were examined in 143 meningiomas from patients aged ≤50 years, comprising 62 fresh-frozen tissues collected during 1999-2003 (Period 1) and 81 formalin-fixed paraffin-embedded tissues from 2006-2023 (Period 2).

RESULTS: Three SNPs were detected in 9 of 143 meningiomas (6.3%). While the differences did not reach statistical significance (p > 0.05), minor allele frequencies of all three SNPs were reduced two- to four-fold in Period 2 compared with Period 1. The observed frequencies were similar to those reported in Japanese cohorts but substantially lower than the ≥30% reported in European populations.

CONCLUSION: Despite the limitation of using tumour-derived DNA to assess germline variants, our findings consistently showed that MLLT10 risk SNPs occur at very low frequencies in Koreans, similar to Japanese data and in contrast to Europeans. These results highlight the population-specific nature of MLLT10 variants and underscore the need for large-scale Asian studies for risk SNP analysis in meningiomas.

PMID:42059173

Malays J Pathol. 2026 Apr;48(1):53-61.

ABSTRACT

INTRODUCTION: The COVID-19 pandemic has caused a rise in secondary infections, including invasive fungal diseases (IFDs), which have greatly increased morbidity and mortality. This study aimed to explore the demographics, risk factors and outcomes of IFDs in COVID-19 patients admitted to our centre.

MATERIALS AND METHODS: We retrospectively reviewed data from PCR-confirmed category 4 or 5 COVID-19 patients between 2020 and 2023 who also had positive mycology cultures or serology. Patients with positive fungal tests more than 90 days after their initial COVID-19 diagnosis were excluded.

RESULTS: Among 5,075 PCR-positive COVID-19 patients, 23 (0.45%) met the criteria. Of these, 15 (65.2%) had candidiasis, seven (30.4%) aspergillosis, and one (4.3%) Exophiala fungaemia. No mucormycosis cases were identified. The male-to-female ratio of IFDs was 2.8:1, with ages ranging from 26 to 77 years (mean 59.6). The interval between COVID-19 diagnosis and positive fungal test ranged from 3 to 38 days, averaging 12.6 days for candidiasis and 16 days for aspergillosis (difference not statistically significant). Only acute kidney injury was significantly linked to candidiasis. Common factors across all cases included indwelling vascular catheters (95.7%), ICU admission (91.3%), mechanical ventilation (87%), lung diseases (65.2%), kidney impairment (60.9%), poorly controlled diabetes (34.8%), and liver impairment (26.1%). Overall mortality was 91.3% (100% for aspergillosis and Exophiala fungaemia, 86.7% for candidiasis).

CONCLUSION: Although IFD prevalence in COVID-19 patients is low, its high morbidity and mortality make it a critical concern. Early identification of risk factors may help reduce its occurrence and improve outcomes.

PMID:42059167

Liver Int. 2026 Jun;46(6):e70620. doi: 10.1111/liv.70620.

ABSTRACT

BACKGROUND: Previous exposure to hepatitis B virus (HBV) may influence the risk of developing hepatocellular carcinoma (HCC) and other liver-related events (LRE), in particular in patients after HCV cure. Previous studies were not conclusive and there are only few large studies on this topic from Europe.

METHODS: We analysed clinical endpoints (≥ 3-point increase in MELD score, oesophageal variceal bleeding, ascites, encephalopathy, liver transplantation, death, with/without HCC; HCC alone) in patients cured from HCV. Data were obtained from the German Hepatitis C Registry. Patients after organ transplantation, a history of HCC, HIV co-infection, or HBsAg positivity were excluded. A subanalysis was conducted in patients with cirrhosis. Statistical analyses included logistic regression to identify predictors of clinical endpoints and Kaplan-Meier curves to analyse the influence of HBV serological markers.

RESULTS: A cohort of 6198 patients fulfilled inclusion criteria, the median time of follow-up was 2.5 years (range 0.04-8.01). Serological evidence of previous HBV exposure was present in 1889 patients (anti-HBc positive). In patients with cirrhosis, univariate analyses identified anti-HBc positivity (odds ratio [OR], 1.48), cirrhosis (OR, 4.89), features of portal hypertension (ascites (OR, 5.66), oesophageal varices (OR, 4.88)), diabetes (OR, 3.23), and malignancies (OR, 10.34) as risk factors for composite LRE. In multivariable analysis, anti-HBc positivity (OR, 1.53) and cirrhosis (OR, 4.63) remained independent risk factors for the composite endpoints, whereas anti-HBc positivity was not associated with HCC or Kaplan-Meier survival analyses.

CONCLUSIONS: Resolved HBV infection was not associated with the development of HCC or survival in Caucasians after HCV cure. Although anti-HBc positivity was linked to composite outcomes, its clinical relevance appears limited.

TRIAL REGISTRATION: The registry was registered at the German Clinical Trials Register (DRKS; IDDRKS00009717).

PMID:42059159 | DOI:10.1111/liv.70620